tbuckley/cabot-search huggingface dataset:
QOL-34. The relationship between Psychological Flexibility, Quality-of-Life and psychological health in young people who have experienced a brain tumour
Authors: Jac Airdrie, Chloe Geagan, Nicholas Davies, Katie Powers, Ingram Wright, Heather Borrill, Faith Gibson, Steve Clifford, Stephen Lowis, Simon Bailey, Jennifer Limond, Ray Owen, Richard Grundy, James Lemon, Louise Hayes, Sam Malins, Sophie Thomas
Journal: Neuro-Oncology (2022)

Abstract Despite increasing survival rates in young people who have experienced a brain tumour, this patient group have the poorest reported quality-of-life (QoL) of all cancer survivors. QoL is defined as an individual’s perception of their position in life in relation to their goals, expectations and standards. QoL can be influenced by physical functioning but one of its strongest predictors is psychological health. A concept that has a large impact on psychological health is Psychological Flexibility (PF). PF refers to the ability to recognise and adapt to situations, shift cognitive and behavioural repertoires which are impacting negatively on personal and social functioning and commit to behaviours that are in line with strongly held values. Studies have demonstrated a relationship between PF and QoL in other patient populations such as chronic pain and breast cancer survivors. In this study we explored the relationship between PF and QoL at baseline in a sample of young people enrolled in a randomised controlled trial of Acceptance and Commitment Therapy (ACT) for young people who have experienced a brain tumour. We found that higher PF was associated with higher QoL in both 11-15 year olds (R2 = .69, p &amp;lt; .05) and 16 – 24 year olds (R2 = .29, p &amp;lt; .01). We also found higher PF was associated with lower levels of mental health difficulties (R2s ≥ .24, ps &amp;lt; .01) which was also associated with higher levels of QoL (R2 = .49 , p &amp;lt; .01). The results suggest assessing and providing support to increase PF is important for young people who have experienced a brain tumour. It highlights that interventions found to increase PF, such as ACT, could be helpful in improving psychological health in this population.
Dexamethasone and brain metastasis-infiltrating CD8+ T cells.
Authors: Lisa Sudmeier, Kimberly B. Hoang, Edjah Nduom, Subir Goyal, Yuan Liu, Jeffrey J. Olson, Suresh S. Ramalingam, Rafi Ahmed
Journal: Journal of Clinical Oncology (2022)

e15075 Background: Nearly all patients who develop large and/or symptomatic brain metastases receive corticosteroids such as dexamethasone (Dex) to treat or prevent symptoms like nausea, headaches, or focal neurologic deficits. Dex has immunosuppressive effects such as induction of T cell apoptosis, so it’s possible that this treatment may impair the anti-tumor immune response. To address this question, we performed a secondary analysis of our in-press data describing the phenotype of brain metastasis-infiltrating CD8+ T cells to determine whether the duration of Dex therapy prior to surgical resection correlated with phenotypes we described our cohort. Methods: Fresh brain metastases specimens were weighed, and immune cells were isolated. CD45+ and CD8+ lymphocytes were counted via flow cytometry from 35 and 34 samples, respectively. A subset of samples were analyzed by high-parameter spectral flow cytometry to gain phenotypic information. Dex treatment was later extracted from the electronic medical record, and Spearman’s correlation coefficients (CC) were calculated to evaluate the association between duration of Dex therapy and brain metastasis-infiltrating lymphocyte density or phenotype. Results: Patients were on Dex for a median of 3 days (4mg q6 hours) prior to surgery. On univariate analysis, the CC between CD45+ lymphocytes or CD8+ T cells per gram of tumor and duration of Dex treatment was -0.185 (P=0.288) and -0.122 (P=0.49), respectively. The CC between frequency of PD-1+ CD8+ T cells and duration of Dex was -0.064 (p=0.784, 21 patients). In our previous work, we used the FLOWSOM algorithm to identify distinct populations of CD8+ T cells that were enriched in brain metastases compared to blood. We described two such populations, one with a tissue residence phenotype, and the other with terminally-differentiated phenotype. The CC between frequency of these populations and duration of Dex was 0.043 (p=0.889) and 0.238 (p=0.433), respectively (13 patients). We also tested for correlation between frequency of individual PD-1+ CD8+ T cell populations and duration of Dex treatment (13-18 patients). The CC for Tim3+, CD39+, CTLA4+, CD127+, Tcf-1+, CD28+, and GZMB+ populations of PD-1+ CD8+ T cells were 0.037 (p=0.891), 0.096 (p=0.705), -0.094 (p=0.738), 0.011 (p=0.971), -0.026 (p=0.918), 0.384 (p=0.128), and 0.236 (p=0.358), respectively. Conclusions: Within this cohort of patients who were on Dex for a median of 3 days prior to surgery, duration of pre-surgery Dex did not significantly affect density of brain metastasis-infiltrating CD45+ lymphocytes or CD8+ T cells or frequency of PD-1+ CD8+ T cells.
Genomic characterization of primary cervical cancer and lung metastasis.
Authors: Huarong Tang, Zhuomin Yin, Hanmei Lou, Yangyang Yu, Yunjie Song, Mingzhe Xiao, Chuang Qi
Journal: Journal of Clinical Oncology (2022)

e17527 Background: Cervical cancer ranks fourth in incidence and mortality among female tumors in the world. Lung metastases are the most common metastatic foci of cervical cancer, which were associated with poor prognosis. Exploring the different genomic landscape between primary tumor and lung metastasis would help to understand the mechanism of cervical cancer lung metastasis. Methods: A total of 52 Chinese cervical cancer patients with lung metastasis were enrolled between 2016 and 2020. Among whom 37 patients had paired samples (primary tumor and lung metastasis), 6 had only primary tumor samples, and 9 had only lung metastasis samples. Lung metastasis samples were confirmed as cervical cancer metastasis via immunohistochemistry. All the formalin-fixed paraffin-embedded (FFPE) tumor samples and matched peripheral blood were collected and underwent whole-exome sequencing (WES). The Illumina NovaSeq 6000 (Illumina, San Diego, CA, USA) sequencing platform was used to perform 150-nt paired-end multiplex sequencing of DNA samples. The average coverage depth was 340× in FFPE samples and 170× in white blood cell controls. Normally distributed data were compared using the t-test and data with abnormal distribution were compared using the Mann–Whitney U test. Results: There were 4,212 and 6,341 somatic mutations in primary tumor and lung metastasis, respectively. The consistencies for SNVs/indels and CNVs were 41.22% (2.86%–76.11%) and 13.65% (3.69%–76.11%). The most frequently altered genes in primary tumor and lung metastasis were PIK3CA (23.26% vs. 36.96%; p = 0.26), TTN (23.26% vs. 39.96%; p = 0.18), MUC4 (16.28% vs. 39.96%; p = 0.03), ARMCX4 (25.58% vs. 26.09%; p = 1), and MUC16 (18.60% vs. 26.09%; p = 0.45). MUC4 had a significantly higher mutation frequency in lung metastasis than in primary tumor. To explore the mutation characteristics, co-mutations in primary tumor and lung metastasis were analyzed. EP300/MUC16 co-mutation (p &lt; 0.01) was identified in primary tumor. KMT2D/MUC16 co-mutation (p &lt; 0.01) was identified in lung metastasis. Among the paired samples, the Cosmic Signature analysis had shown that Signature 2, which was attributed to activity of the AID/APOBEC family of cytidine deaminases, was higher in lung metastasis than primary tumor (p = 0.042). Meanwhile, the amplification of 17q12 was more frequently observed in lung metastasis in contrast to primary tumor (p = 0.035). Furthermore, the GO/KEGG analysis had revealed that the mutant genes which only observed in lung metastasis were significantly enriched in ATPase activity and inositol phosphate metabolism. Conclusions: In summary, comprehensive genomic profiling of primary cervical cancer and lung metastasis can be of help to identify metastasis-specific features and understand the mechanism of cervical cancer lung metastasis.
Intestinal-targeted nanotubes-in-microgels composite carriers for capsaicin delivery and their effect for alleviation of Salmonella induced enteritis
Authors: Yu Yuan, Ying Liu, Yang He, Bingkun Zhang, Liang Zhao, Simin Tian, Qimeng Wang, Shanan Chen, Zekun Li, Shuang Liang, Guohua Hou, Bin Liu, Yuan Li
Journal: Biomaterials (2022)
Prognostic role of preoperative chemosensitivity in patients with non–small cell lung cancer (NSCLC) treated with preoperative chemotherapy: A study of National Cancer Database (NCDB).
Authors: Lei Deng, Changchuan Jiang, Stuthi Perimbeti, Hongbin Chen
Journal: Journal of Clinical Oncology (2022)

8538 Background: Response to preoperative systemic therapy may provide valuable information regarding tumor biology and prognosis. This is increasingly relevant nowadays considering the promising results from preoperative chemoimmunotherapy. This study aims to examine the prognostic role of preoperative chemosensitivity defined by TNM stage change in NSCLC. Methods: Patients with histologically confirmed clinical stage II-III NSCLC who have received preoperative chemotherapy followed by R0 curative surgery were identified in the NCDB between 2006 and 2017. Patients who have developed metastasis at the time of surgery, received any perioperative radiotherapy or single agent chemotherapy, or died within 90 days of surgery, were excluded. Preoperative chemosensitivity is categorized as ypT0N0, downstaged (pTNM &lt; cTNM, excluding ypT0N0), and not downstaged (pTNM ≥ cTNM). Logistic regression was used to evaluate associations between chemosensitivity and demographic, clinical, and pathological factors. Log-rank was used for survival analysis and adjusted by cox regression for age, gender, race, year of diagnosis, academic center, insurance, comorbidity, histology, and clinical stage. Results: A total of 1266 patients were included, of whom 104 (8.2%) had ypT0N0, 575 (45.4%) were downstaged, while 587 (46.4%) were not. Female, diagnosis in recent years, treatment at academic centers, and squamous histology were significantly associated with better chemosensitivity, while clinical TNM stage, age, race, and comorbidity were not. Five-year overall survival rate is 81.2%, 57.7%, and 46.2%, respectively (log-rank p &lt; 0.001). After Cox regression adjustment, compared with not downstaged, ypT0N0 (HR 0.28, 95% CI 0.17 – 0.45) and downstaged (HR 0.61, 95% CI 0.51 – 0.74) were independently associated with improved postoperative survival. Conclusions: Preoperative chemosensitivity defined by TNM stage change before and after chemotherapy may prognosticate NSCLC after curative surgery. It may be a useful clinical tool to identify patients with high risk of treatment failure after neoadjuvant chemoimmunotherapy in the future.[Table: see text]
Molecular subtype to predict pathologic complete response in HER2-positive breast cancer in the I-SPY2 trial.
Authors: Alexandra Thomas, Amy Sanders Clark, Christina Yau, Denise M. Wolf, Laura van 't Veer, Emily H. Douglas, Amy Jo Chien, Laura Ann Huppert, Hope S. Rugo, Rebecca Arielle Shatsky, Claudine Isaacs, Donald A. Berry, Douglas Yee, Angela DeMichele, Laura Esserman
Journal: Journal of Clinical Oncology (2022)

510 Background: HER2-positive breast cancer (bc) is a very heterogenous disease. We hypothesized that molecular subtype may predict disease response to investigational agents in HER2+ bc. Here, we report the pathologic complete response (pCR) rate in the first six agents tested in HER2+ bc in the I-SPY 2 trial for the full HER2+ cohort, by molecular subtype, and by disease receptor status. Methods: Women with HER2+ tumors which were &gt; 2.5 cm were eligible. The I-SPY2 platform trial tests novel agents given neoadjuvantly with a backbone of taxol (T) and trastuzumab (H) followed by doxorubicin and cyclophosphamide. Agents investigated in HER2+ bc were TH (control), MK2206, AMG386, pertuzumab (P), neratinib (N (given in place of H), and TDM1+P (given in place of TH). An investigational arm graduated if there was &gt;85% chance of success compared to control in a 300-person phase 3 neoadjuvant trial. Further details of the I-SPY2 methods have been previously published. Molecular subtyping based on gene expression was utilized to categorize tumors into 5 response predictive subtypes (RPS) (HER2-/Immune-/DRD (DNA repair deficiency)-, HER2-/Immune+, HER2-/Immune-/DRD+, HER2+/Her2_or_Basal and HER2+/Luminal). Results: For the full HER2+ cohort (N=245) pCR rate was higher in all investigational arms than control (Table). By tumor receptor status, HER2+/HR- tumors (N=89) had a higher pCR rate than HER2+/HR+ tumors (N=156; 63% vs 37%, p = 0.0001). In HER2+/HR- tumors N, MK2206, P and TDM1/P graduated. In HER2+/HR+ tumors P and TDM1/P graduated. 76% (185/245) of I-SPY 2 HER2+ patients were classified as HER2+/Her2_or_Basal and 24% (60/245) were HER2+Luminal. pCR rate was significantly higher in the HER2+/Her2_or_Basal group than in the HER2+/Luminal group (57% vs 15%, p &lt; 0.0001). All agents, except for MK2206, where numbers were small, showed greater efficacy in the HER2+/Her2_or_Basal group than in the HER2+/Luminal group. HER2+/Luminal appeared to be more sensitive to the AKT inhibitor MK2206 than to targeted HER2 agents, though numbers are small. Conclusions: pCR rates for patients with HER2+ bc treated with investigational agents, particularly dual HER2-blockade, were promising. Molecular response predictive subtype classification provides insight on how to better target therapy. The HER2+/Luminal group had low pCR rates with dual HER2-blockade but may have higher pCR rate with the addition of an AKT inhibitor and identifies a subgroup of HER2+ tumors in need of novel approaches. AKT inhibition for HER2/Luminal is being tested in I-SPY 2.2. Clinical trial information: NCT01042379. [Table: see text]
Long-term prospective results of the Spanish multicentre experience using recirculant hyperthermic MMC with Combat BRS HIVEC system
Authors: F. Guerrero-Ramos, A. Plata-Bello, A. González-Díaz, C. García, I. González-Valcárcel, J.M. De La Morena-Gallego, F.J. Díaz-Goizueta, J. Fernández-Álamo, V. Gonzalo, J. Montero, A. Sousa-Escandón, J. León, J.L. Pontones, F. Delgado, M. Adriazola, Á. Pascual, J. Calleja, A. Ruano, L. Martínez-Piñeiro, J. Angulo-Cuesta
Journal: European Urology (2022)
Reply to: Hultström et al., Genetic determinants of mannose-binding lectin activity predispose to thromboembolic complications in critical COVID-19. Mannose-binding lectin genetics in COVID-19
Authors: Rosanna Asselta, Elvezia Maria Paraboschi, Matteo Stravalaci, Pietro Invernizzi, Paolo Bonfanti, Andrea Biondi, Isabel Pagani, Mattia Pedotti, Andrea Doni, Francesco Scavello, Sarah N. Mapelli, Marina Sironi, Chiara Perucchini, Luca Varani, Milos Matkovic, Andrea Cavalli, Daniela Cesana, Pierangela Gallina, Nicoletta Pedemonte, Valeria Capurro, Nicola Clementi, Nicasio Mancini, Rafael Bayarri-Olmos, Peter Garred, Rino Rappuoli, Stefano Duga, Barbara Bottazzi, Mariagrazia Uguccioni, Elisa Vicenzi, Alberto Mantovani, Cecilia Garlanda
Journal: Nature Immunology (2022)
LGG-11. Analysis of neurosurgical complications in pediatric supratentorial midline low-grade glioma – results from the German LGG studies
Authors: Sarah Weiß, Matthias Schulz, Daniela Kandels, Pablo Hernáiz Driever, Olaf Witt, Ulrich-Wilhelm Thomale, Astrid Gnekow, Michè le Simon
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: Around 80% of all pediatric low-grade glioma (LGG) patients undergo at least one tumor surgery. Interventions in the supratentorial midline (SML) are particularly challenging due to the proximity of eloquent areas, yet associated complications are scarcely reported. We investigated the frequency of neurosurgical complications and related impairments and aimed at identifying risk factors for their appearance related to patient characteristics or the procedure. PATIENTS AND METHOD: Records were retrospectively analyzed from 321 patients with SML-LGG from the successive multicenter German LGG studies, who underwent neurosurgery at 63 hospitals between May 12th,1998 and June 27th, 2020. RESULTS: 543 operations (235 resections, 168 biopsies, 140 non-tumor interventions) were performed on 321 patients (54% male, median age 9 years, 11% NF1 positive, 43% visual pathway glioma). Surgical mortality rate was 0,93% (n=3). Applying the Drake classification postoperative surgical morbidity was observed in 259 cases (47,7%), medical morbidity in 103 cases (19%). 30-day persistence rate of newly developed neurological deficits was 44,8% (65/165 cases); neuroendocrine impairment affected 57 patients (17,8%), visual deterioration 34 (10,6%). Complications/impairments following resections were associated with patient age below 3 years at operation, tumor volume above 80 cm3, presence of hydrocephalus prior to surgery, complete resection, intervention in centers with fewer reported resections and surgery performed between 1998-2006 by univariate analysis. In contrast, the neurosurgical approach, tumor location, NF1 status as well as previous antineoplastic treatment were not associated with the frequency of complications. Regarding biopsies, open biopsies showed significantly more surgery-associated complications/impairments compared with stereotactic procedures. CONCLUSIONS: Neurosurgery-associated complications and impairments were frequent in pediatric patients with supratentorial midline LGG undergoing open surgery in the German LGG-studies. We identified six patient- and institution-associated factors that may increase the risk for surgical complications. Skills at the treating center and extent of resection should be considered appropriately prior to intervention.
A colorectal biomarker think tank collaborative: Devising solutions for patients, caregivers, and cancer care teams.
Authors: Kim Newcomer, Andrea Goodman, Negeen Fathi, Abdullah Shoeb
Journal: Journal of Clinical Oncology (2022)

e15507 Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. With more than a dozen known mutations in colorectal cancer, and growing knowledge about different efficacy of drug options dependent on biomarker status, biomarker testing and results can aid in more effective and lifesaving treatment planning specifically for the unique characteristics of each individual’s tumor. However, biomarker testing in colorectal cancer remains low, and the Colorectal Cancer Alliance aims to increase knowledge and awareness of testing among patients and their care teams. Methods: In 2019, the Alliance distributed an online survey to assess patient, survivor, and caregiver knowledge and understanding of biomarker testing. The results identified patient confusion, suboptimal biomarker testing rates, and critical aspects of patients' medical treatment plan. To further understand identified gaps, the Alliance recruited a diverse set of patients and caregivers at various stages of colorectal cancer for a focus group in 2021 to explore understanding around biomarkers, treatment pathways, biomarker testing decisions, and gaps around current testing and re-testing processes. Working with an expert Advisory Committee, the Alliance utilized findings from the survey and focus group to plan a 2021 Summit focused on identifying solutions for known barriers. Results: Summit participants discussed innovative and evidence-based solutions focused on three audiences: patients, caregivers, and cancer care team members, to close some of the gaps identified previously. Patient solutions focused on cancer field-wide collaborations to create standard language and health literacy standards for biomarkers and testing that allow for clear, transparent notes, patient engagement, and shared decision making. Caregiver solutions focused on elevating the caregiver role as an advocate through updated telehealth infrastructure that allows for caregiver support in the journey. Cancer care team solutions focused on utilizing continuing medical education (CME) courses to create standard health literacy standards, become better advocates for biomarker testing, and create multidisciplinary discussion opportunities between health professionals. Conclusions: Patients and caregivers are overwhelmed by the complexity and variety of treatment options. It is critical that we put swift, collaborative solutions in place with efforts to improve resources, shared language, infrastructure, and advocacy to empower cancer care teams, patients and caregivers alike. We aim to increase knowledge of and access to guideline-concordant biomarker testing, so that patients, caregivers, and cancer care teams can make informed treatment decisions accordingly, and understand the choices and discussions at each step.
Ethnic disparities in adverse events of radiotherapy for breast cancer: A scoping review.
Authors: Siddhi Hegde, Ruth C Carlos
Journal: Journal of Clinical Oncology (2022)

e18502 Background: Ethnic disparities have been well-documented in the US as a contributor to poor outcomes following radiotherapy in ethnic minorities. The objective was to examine the intra-group and inter-group ethnic differences in adverse effects experienced by Asian breast cancer patients undergoing radiotherapy. Methods: A scoping review involving the Pubmed database was conducted. The search strategy included a combination of keywords and index terms related to Asians, breast cancer, CTCAE and treatment. Title, abstract and then full-text screening was performed by two reviewers. Primary research studies and systematic review articles involving female adults in peer-reviewed articles or grey literature records, of any design or date and published in English, were included. Descriptive statistics and charting was used to summarize the results. Results: Of 1765 abstracts retrieved and screened, 37 articles were ultimately included for analysis. The majority of the studies involved Japanese patients (40.5%) followed by Chinese patients (24.3%) with an average of 468 patients being studied per study (ranging from 1-4,869 patients). Only a single study was conducted in the US. 35.1% of studies reported ethnicity and 64.8% of studies reported Asian ethnic subgroups. Most patients underwent whole-breast irradiation (62.1%). 37.5% of studies involved patients with TNM stages I-III breast cancer. Most patients were postoperatively enrolled after BCS (59.4%).ER/PR status was reported in most studies (54.1%) with an average of 553 patients being positive for either hormone receptor and averages of 210 and 905 patients each in studies where numbers were reported individually. HER-2 status was reported in 48.7% of studies with an average of 28 positive HER-2 patients in each study. Most studies reported skin toxicity following radiotherapy (81.1%), commonly grade 1 or 2 (40.5% each) affecting an average of 46% of patients in each study. These dermatological adverse events were radiation dermatitis, hyperpigmentation, fibrosis, hypertrophic scarring or erythema. Conclusions: Ethnicity was under-reported in the studied literature involving breast cancer treatment. Strategies to improve reporting of ethnic subgroups in literature and to reduce psychosocial barriers to access and treatment with a specific focus on mitigating dermatological adverse events of radiotherapy in Asian breast cancer patients may improve overall outcomes in this group.